Project Summary/Abstract This application is for a shared instrumentation grant from the Light Microscope Imaging Facility at Case Western Reserve University (CWRU) School of Medicine (SOM) to acquire a fully automated, high-capacity, high- resolution Hamamatsu Nanozoomer S60 slide scanner that can accommodate both brightfield and fluorescence imaging in single-slide and double-slide formats. We also request MicroDimensions 3D reconstruction and alignment software packages for manipulating and analyzing the whole slide images produced with the scanner. We need to replace a scanner that is not functioning properly. Our well-established shared core facility supports NIH-funded investigators by giving them access to state-of-the-art microscopy technologies that enhance collaborative, multidisciplinary research. Acquisition of this instrument will have a high impact on the biomedical research at CWRU and expand the scope of our NIH-funded projects. Several projects have been identified that will utilize the scanner and its associated analyses programs. These include: the genetic mechanisms underlying skin fibrosis and cranial bone development (Atit); the mechanisms behind the lifelong functions of transcription factors in axonal growth and architecture (Deneris); deep-learning for histologic image predictors of various diseases (Madabhushi); the development of diagnostic probes to discriminate between glioma subtypes for screening and survival therapies (Brady-Kalnay); the role of progesterone receptors in the control of parturition and the development of therapies to prevent preterm birth (Messiano); the mechanisms by which breast cancer stem cells overcome metastatic latency leading to disease recurrence and the biomarkers that could potentially identify those tumors likely to undergo this process (Schiemann); and the significance of cholesterol-related proteins in brain and retinal function (Pikuleva). Many additional projects of minor users and others at CWRU are anticipated. All of the proposed projects are in need of a high-capacity automated scanner acquiring whole slide images so that analyses can be applied to tissues that cover hundreds of fields of view, rather than the single regions of interest that can be acquired on a standard microscope.